Marinopyrroles were first reported to show antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA) in 2008 (Hughes et al., “The marinopyrroles, antibiotics of an unprecedented structure class from a marine Streptomyces sp.” Org Lett 10:629-631, 2008). Due to their novel class of molecular structures and promising biological properties, the marinopyrroles have attracted considerable attention. The first total synthesis of (±)-marinopyrrole A was reported along with 12 derivatives in early 2010 (Cheng et al., “Total synthesis of (±)-marinopyrrole A and its library as potential antibiotic and anticancer agents,” J Comb Chem 12:541-547, 2010). Synthesis of (±)-marinopyrrole A via an intermolecular Ullman coupling reaction as a key step to form bispyrrole system was published by Kanakis and Sarli five months later (Kanakis et al., “Total synthesis of (±)-marinopyrrole A via copper-mediated N-arylation,” Org Lett 12:4872-4875, 2010). In 2011, Nicolaou's group published a new five-step method to access marinopyrrole derivatives as well as (+)- and (−)-atropisomer after a chiral separation of (±)-marinopyrrole A using chiral HPLC and their antibiotic activities against MRSA (Nicolaou et al., “Total synthesis and biological evaluation of marinopyrrole A and analogues,” Tet Lett 52:2041-2043, 2011). Recently, the synthesis of a novel series of “asymmetrical” marinopyrrole derivatives with superior antibiotic activities against MRSA to that of the parent marinopyrrole A was revealed (Liu et al., “Marinopyrrole derivatives as potential antibiotic agents against methicillin-resistant Staphylococcus aureus (I),” Mar Drugs 10:953-962, 2012). Most recently, Moore's group published biosynthesis of marinopyrrole A via a N,C-bipyrrole homocoupling catalyzed by two flavin-dependent halogenases (Yamanaka et al., “Flavoenzyme-catalyzed atropo-selective n,c-bipyrrole homocoupling in marinopyrrole biosynthesis,” J Am Chem Soc 134:12434-12437, 2012).
The global crisis of antibiotic resistance has spread rapidly over the last several decades. MRSA infections have reached epidemic proportions in many countries and represent the most common cause of skin and soft tissue infections in the United States (Grundmann et al., “Emergence and resurgence of methicillin-resistant Staphylococcus aureus as a public-health threat,” Lancet 368:874-885, 2006; Como-Sabetti et al., “Community-associated methicillin-resistant Staphylococcus aureus: trends in case and isolate characteristics from six years of prospective surveillance,” Public Health Rep 124:427-435, 2009). Both hospital-associated and community-associated MRSA can exhibit broader resistance to multiple classes of antibiotics (Chambers et al., “Waves of resistance: Staphylococcus aureus in the antibiotic era,” Nat Rev Microbiol 7:629-641, 2009; Deleo et al., “Community-associated methicillin-resistant Staphylococcus aureus,” Lancet 375:1557-1568, 2010; Lowy, “Antimicrobial resistance: the example of Staphylococcus aureus,” J Clin Invest 111:1265-1273, 2003). Hospital-associated MRSA infections are common among healthcare facilities and are resistant to many antibiotics. However, community-associated MRSA strains are highly virulent and infect even healthy individuals; the incidence of these infections has skyrocketed in the last decade. The relative abandonment of antibiotic discovery and development by the pharmaceutical industry has created a vacuum in the introduction of new antibiotics to treat these increasingly problematic infections. Except for the addition of the oxazolidinone linezolid in 2000, the lipopeptide daptomycin in 2003, and FDA's recent approval of ceftaroline (Teflaro) as an injectable antibiotic to treat adults with community acquired bacterial pneumonia and acute bacterial skin and skin structure infections including MRSA, a very limited number of new antibiotics have been discovered over the last half a century, with only two new classes of anti-MRSA drugs having been approved in the last 40 years. Clearly, novel agents for the treatment of MRSA infections are urgently needed (Butler et al., “Natural products—the future scaffolds for novel antibiotics?” Biochem Pharmacol 71:919-929, 2006). The compositions and methods disclosed herein address these and other needs.